Some chromium(VI) compounds are documented human carcinogens but the exact mechanism of Cr-induced cancer is unknown. Cr(VI) can cross cell membranes but most extracellular Cr(VI) is rapidly reduced to non-toxic Cr(lll) not entering cells, Cr(III) is an important trace element and Cr(III) based compounds are used as dietary supplements. However, intracellular Cr(VI) is unreactive with macromolecules whereas its reductive intermediates, Cr(V), Cr(IV) and Cr(III) bind to macromolecules and are implicated in chromium genotoxicity. Thus, oxidation state determination of intracellular Cr will provide important information relevant to exposure and risk assessment, and for understanding the mechanism of Cr carcinogenesis. The applicants propose measuring the intracellular oxidation state of Cr using x-ray absorption near-edge structure (XANES) spectroscopy. Until now, the XANES technique was not very practical, relying on costly synchrotrons. This attractive technique could be implemented using a lower power cost-effective system incorporating a revolutionary toroidal crystal optic. In this project, a toroidal crystal optic will be designed and fabricated for focusing and monochromatizing x-ray photons with energy near the Cr K-edge. The K-edge XANES spectra for Cr(III) and Cr(VI) standards will be obtained using a compact x-ray tube. The feasibility of the XANES will be evaluated for oxidation state determination of chromium in human cells. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE